TSLP receptor

Class

TSLP pathway inhibitor

The thymic stromal lymphopoietin (TSLP) receptor is a cell-surface complex expressed on immune cells such as dendritic cells, mast cells, and group 2 innate lymphoid cells (ILC2s). It is activated by TSLP, a cytokine released by epithelial cells lining the airways, skin, and gut when these barrier tissues encounter irritants, allergens, or pathogens. TSLP is considered an 'alarmin' because it sits near the top of the signaling cascade that drives type 2 inflammation, the pattern of immune activity characterized by production of interleukin-4, interleukin-5, and interleukin-13, and by recruitment of eosinophils and mast cells. Blocking the TSLP receptor prevents TSLP from initiating this cascade regardless of which downstream cytokines a given patient's inflammation depends on, which is biologically attractive in diseases where type 2 inflammation is heterogeneous. This mechanism is relevant across a range of conditions where epithelial barriers are chronically irritated and downstream type 2 immunity drives symptoms, including asthma, chronic obstructive airway disease, atopic dermatitis, and related inflammatory conditions of barrier tissues. Because the receptor lies upstream of multiple effector pathways, its inhibition can be a broader intervention than agents that neutralize a single downstream cytokine.